The transcription factor NF-kappaB is a critical regulator of inflammatory and cell survival signals. Proteasomal degradation of NF-kappaB subunits plays an important role in the termination of NF-kappaB activity, and at least one of the identified ubiquitin ligases is a multimeric complex containing Copper Metabolism Murr1 Domain 1 (COMMD1) and Cul2. We report here that GCN5, a histone acetyltransferase, associates with COMMD1 and other components of the ligase, promotes RelA ubiquitination, and represses kappaB-dependent transcription. In this role, the acetyltransferase activity of GCN5 is not required. Interestingly, GCN5 binds more avidly to RelA after phosphorylation on Ser 468, an event that is dependent on IKK activity. Consistent with this, we find that both GCN5 and the IkappaB Kinase (IKK) complex promote RelA degradation. Collectively, the data indicate that GCN5 participates in the ubiquitination process as an accessory factor for a ubiquitin ligase, where it provides a novel link between phosphorylation and ubiquitination.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666342PMC
http://dx.doi.org/10.1101/gad.1748409DOI Listing

Publication Analysis

Top Keywords

gcn5 required
8
ubiquitin ligase
8
gcn5
6
required cofactor
4
cofactor ubiquitin
4
ligase targets
4
targets nf-kappab/rela
4
nf-kappab/rela transcription
4
transcription factor
4
factor nf-kappab
4

Similar Publications

Advances of NAT10 in diseases: insights from dual properties as protein and RNA acetyltransferase.

Cell Biol Toxicol

December 2024

Department of Laboratory Medicine, Affiliated Qingyuan Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, Guangdong, China.

N-acetyltransferase 10 (NAT10) is a member of the Gcn5-related N-acetyltransferase (GNAT) family and it plays a crucial role in various cellular processes, such as regulation of cell mitosis, post-DNA damage response, autophagy and apoptosis regulation, ribosome biogenesis, RNA modification, and other related pathways through its intrinsic protein acetyltransferase and RNA acetyltransferase activities. Moreover, NAT10 is closely associated with the pathogenesis of tumors, Hutchinson-Gilford progeria syndrome (HGPS), systemic lupus erythematosus, pulmonary fibrosis, depression and host-pathogen interactions. In recent years, mRNA acetylation has emerged as a prominent focus of research due to its pivotal role in regulating RNA stability and translation.

View Article and Find Full Text PDF

Reversible lysine acylation (RLA) is a conserved posttranslational modification that cells of all domains of life use to regulate the biological function of proteins, some of which have enzymatic activity. Many AMP-forming organic acid:CoA ligases are regulated acylation in prokaryotes and eukaryotes. Here, we report the acetylation of the -succinylbenzoyl-CoA synthetase (EC 6.

View Article and Find Full Text PDF
Article Synopsis
  • - Despite advancements in treatment, multiple myeloma (MM) is still an incurable cancer, with gaps in understanding the epigenetic mechanisms that contribute to its development and progression.
  • - The study focuses on the SAGA complex, particularly the ADA2B subunit, which plays a critical role in regulating key pathways like MTORC1 signaling and oncogenic programs associated with transcription factors MYC, E2F, and MAF.
  • - The research reveals that targeting SAGA's KAT module and its interaction with specific acetyltransferases could present new therapeutic vulnerabilities in MM, potentially leading to future treatment strategies.
View Article and Find Full Text PDF

Histone acetyltransferases (HATs) modify the amino-terminal tails of the core histone proteins via acetylation, regulating chromatin structure and transcription. GENERAL CONTROL NON-DEREPRESSIBLE 5 (GCN5) is a HAT that specifically acetylates H3K14 residues. GCN5 has been associated with cell division and differentiation, meristem function, root, stem, foliar, and floral development, and plant environmental response.

View Article and Find Full Text PDF

Despite recent advances in therapeutic treatments, multiple myeloma (MM) remains an incurable malignancy. Epigenetic factors contribute to the initiation, progression, relapse, and clonal heterogeneity in MM, but our knowledge on epigenetic mechanisms underlying MM development is far from complete. The SAGA complex serves as a coactivator in transcription and catalyzes acetylation and deubiquitylation.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!